Mid and Long Term Atrio-Ventricular Mechanism in Children after Recovery from Asymptomatic O Mildly Symptomatic Sars Cov2 Infection

Background: Clinical manifestations of children's coronavirus disease-2019 (COVID-19) were initially considered less severe compared with adult patients. However, there is now increasing evidence of a "long-tail" of COVID-19 related symptoms lasting for several months after recovery from the acute infection. Long COVID-19-related symptoms and mechanisms are poorly characterized and understood, with several phenotypes reported, often driven by long-term tissue damage (such as lung, heart and brain) and pathological inflammation due to viral persistence and/or immune deregulation. Purpose(s): The objective of this study was to evaluate atrio-ventricular mechanics, by means of two-dimensional speckle-tracking echocardiography, in previously healthy children recovered from asymptomatic or mildly symptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in a long-term followup. Method(s): We analysed a cohort of 157 paediatric patients, mean age 7 +/- 4 years, who had a confirmed diagnosis of SARS-CoV-2 infection and were asymptomatic or mildly symptomatic for COVID-19. Patients underwent standard transthoracic echocardiogram and speckle tracking echocardiographic study 148 +/- 68 days after diagnosis. One hundred seven age, sex, and body surface area comparable healthy subjects were used as control group. Result(s): Left ventricular ejection fraction was within normal limits in postCOVID-19 cases and CTRL with no significant differences between the two groups (postCOVID-19: 65.6 +/- 4% vs CTRL: 65.0 +/- 5%, p = 0.182).Left ventricular (LV) global longitudinal strain (postCOVID-19: -20.5 +/- 2.9%;CTRL: -21.8 +/- 1.7%;p < 0.001) was significantly reduced in cases compared with CTRLs. An amount of 11 (7%) postCOVID-19 cases showed impaired GLS values < -17% and 95 subjects (60%) presented with a strain lower than -16% in more than 2 segments. These subjects did not show any difference regarding symptoms or serological findings. Moreover, GLS was significantly reduced in children with disease's onset during the second wave of COVID-19 pandemic, compared with those during the first wave (second wave: -20.2 +/- 2.6%;first wave: -21.2 +/- 3.4%;p = 0.048). Finally, peak left atrial systolic strain was within the normal range in the postCOVID-19 group with no significant differences compared to CTRL (postCOVID-19: 49.1 +/- 12%;CTRL: 49.5 +/- 18%). Conclusion(s): SARS-CoV-2 infection may affect left ventricular deformation in children despite an asymptomatic or only mildly symptomatic acute illness. Our data show an amount of 60% of children, recovering from asymptomatic or mildly symptomatic COVID-19, with still mild subclinical systolic cardiac impairment in the midand long-term follow-up after the infection. This subtle impairment was seen to be worse in children recovering from the second wave of COVID-19 compared to the first one. A follow-up is needed to verify the reversibility of these alterations and their impact on long-term outcomes.

Resposta Sorologica Apos Duas Doses Da Vacina Contra Sars-Cov-2 Em Pacientes Com Leucemia Mieloide Cronica

Objetivos: Avaliar as taxas de seroconversao apos duas doses da vacina contra SARS-CoV-2 em pacientes com Leucemia Mieloide Cronica (LMC). Material e Metodos: Foram coletadas amostras para teste sorologico de triagem para avaliacao da presenca de anticorpos IgG (CMIA, SARS-CoV-2 IgM, IgG - Alinity System, Abbott Laboratories, Ireland) no periodo de 1-3 meses apos duas doses de vacina para COVID-19. Nas amostras positivas, foi realizada analise quantitativa de IgG (anti-S1 - SARS-CoV-2 IgG II Quant, Alinity System, Abbott Laboratories, Ireland) e os Titulos de Anticorpos Neutralizantes (TAN), que detectam o efeito citopatico do virus em cultura celular induzidos pelas vacinas (Vero CCL-81 cells). Resultados: Entre agosto e novembro de 2021, foram avaliados 102 pacientes com LMC com media de idade de 56,2 anos (33-85), sendo 58,8% do sexo masculino, 98,5% em Fase Cronica (FC), 80% apresentavam ao menos Resposta Molecular Maior (RMM). 87% dos pacientes estavam em uso de ITQ e 13% estavam em descontinuacao da medicacao. 66,7% receberam a vacina ChAdOx1 nCoV-19 (AZD1222)-Covishield (Oxford/AstraZeneca/Fiocruz), 29,41% CoronaVac (Sinovac/Butatan), 1,96% BNT162b2 (Pfeizer/BioNTech/Fosun Pharma) e 1,96% Ad26.COV2.S (Janssen-Cilag). 15% dos pacientes apresentaram COVID-19 antes da vacinacao. O teste sorologico de triagem (CMIA) foi positivo em 25% dos pacientes. COVID-19 previa foi associada a presenca de anticorpos IgG (p<=0,001). Os TAN foram maiores que 1:320 em 13/26 casos, dentre os quais 5 haviam apresentado COVID-19 antes de completar o esquema vacinal. Neste grupo, 76% receberam a vacina ChAdOx1 nCoV-19, 19% Coronavac e 1% BNT162b2. Dentre os casos com infeccao previa pelo SARS-CoV-2, 7 apresentaram confirmacao laboratorial e 2 tinham quadro clinico sugestivo. Oito casos ocorreram antes da vacinacao e um paciente apresentou quadro leve, apos ter recebido a primeira dose da vacina ChAdOx1 nCoV-19. Onze pacientes estavam em tratamento com Imatinibe, 6 com Dasatinibe e um com Nilotinibe (6 com RMM), 5 em terceira ou quarta linha (sem RMM) e 3 pacientes em descontinuacao de ITQ. A proporcao de pacientes com TAN >1:320 foi superior no grupo que recebia terceira ou quarta linha (p=0,022). Entretanto, neste grupo havia mais pacientes com infeccao previa por COVID-19. Nao houve diferenca estatistica entre as taxas de seroconversao (CMIA, IgM and IgG) entre pacientes que receberam Coronavac ou ChAdOx1 nCoV-19. Nao houve diferencas nas taxas de seroconversao entre pacientes que receberam ITQ e naqueles em descontinuacao (p=0,77). Discussao: Estudos observacionais demonstraram que pacientes com LMC-FC produzem anticorpos em niveis semelhantes a populacao geral, apos receberem as vacinas ChAdOx1 nCoV-19 ou BNT162b2. No estudo conduzido por Rotterdam et al., 100/101 pacientes apresentaram seroconversao apos duas doses. Outro estudo avaliou as taxas de conversao em pacientes que receberam Coronavac, demonstrando menores taxas de conversao se comparados a vacina BNT162b2. Nosso estudo demonstrou que a resposta sorologica apos duas doses de vacina contra SARS-CoV-2 foi menor do que a descrita previamente na literatura. Conclusoes: Nao foram demonstradas diferencas entre os tipos de vacina (Coronavac vs. ChAdOx1 nCoV-19) ou em relacao a fase da doenca na taxa de seroconversao. Duas doses de vacinas para COVID-19 foram insuficientes para imunizacao adequada em pacientes com LMC. Agradecimentos: Brazilian National Council for Scientific and Technological Development (CNPq), grant ndegree 401977/2020-0. Copyright © 2022

Evolution of echocardiographic and cardiac MRI abnormalities during follow-up in patients with previous MIS-C diagnosis

Background and Aim: Growing evidence has documented a severe systemic hyperinflammation syndrome affecting children previ-ously exposed to SARS-CoV-2, known as Multisystem Inflammatory Syndrome in Children (MIS-C). Cardiovascular manifestations in MIS-C are frequent (34%-82%). The aim of our study was to describe the early and late cardiac abnormalities in patients with MIS-C, assessed by standard echocardiography, speckle tracking echocardiography (STE), and cardiac MRI (CMR). Method(s): 32 consecutive patients (21M, 11F), mean age 8.25 +/- 4years (range 1.3-17.7), with confirmed MIS-C diagnosis were enrolled in this study. Clinical, laboratory and microbiological data were collected. At disease onset, all children underwent standard transthoracic echocardiography, STE with analysis of left ventricle global longitudinal strain (GLS) and 23 (75%) of them performed CMR. Patients underwent complete cardiological evaluation, including echocardiography and STE at two months (T1) and six months (T2) after diagnosis. CMR was repeated at six months after diagnosis. Result(s): Cardiovascular symptoms were present in 45.8% of cases. Thirteen children (40.6%) shared Kawasaki Disease-like symp-toms, and 5 (15.6%) needed ICU admission. Early survival was 100%. All patients showed an hyperinflammatory state. Tn-I was elevated in 20 (62.5%) and BNP in 28 (87.5%) patients. Mean LVEF at baseline was 58.8 +/- 10% with 10 patients (31%) below 55%. STE showed reduced mean LV GLS (-17.4 +/- 4%). On CMR, LGE with nonischemic pattern was evident in 8/23 patients (35%). Follow-up data showed rapid improvement of LVEF at T1 (62.5 +/- 7.5 vs. 58.8 +/- 10.6%, p value 0.044) with only three patients (10%) below <= 55% at T1 and one (4%) at T2. LV GLS remained impaired at T1 (-17.2 +/- 2.7 vs.-17.4 +/- 4, p value 0.71), and significantly improved at T2 (-19 +/- 2.6% vs.-17.4 +/- 4%, p value 0.009). LV GLS was impaired (gt;-18%) in 53% of patients at baseline and T1, while only 13% showed persistent LV GLS reduc-tion at T2. Follow-up CMR showed LGE persistence in 33.4% of cases. Conclusion(s): Even though, early cardiac involvement significantly improves during follow-up, subclinical myocardial damage seems to be still detectable 6 months follow up in one third of MIS-C patients.

Evolution of echocardiographic and cardiac magnetic resonance imaging abnormalities during follow-up in patients with multisystem inflammatory syndrome in children.

AIMS: Multisystem inflammatory syndrome in children (MIS-C) with cardiovascular manifestations are frequent. However, there is lacking evidence regarding cardiological follow-up of this cohort of patients. The aim of our study was to describe the early and mid-term cardiac abnormalities assessed by standard and speckle-tracking echocardiography (STE), and cardiac MRI (CMR). METHODS AND RESULTS: We enrolled 32 patients (21 male, 11 female), mean age 8.25 ± 4years, with diagnosis of MIS-C. During admission, all children underwent TTE, STE with analysis of left ventricle global longitudinal strain (GLS) and CMR. Patients underwent cardiological evaluation at 2 (T1) and 6 months (T2) after discharge. Cardiac MRI was repeated at 6 months after discharge. Mean left ventricular ejection fraction (LVEF) at baseline was 58.8 ± 10% with 10 patients (31%) below 55%. Speckle-tracking echocardiography showed reduced mean LV GLS (-17.4 ± 4%). On CMR, late gadolinium enhancement (LGE) with non-ischaemic pattern was evident in 8 of 23 patients (35%). Follow-up data showed rapid improvement of LVEF at T1 (62.5 ± 7.5 vs. 58.8 ± 10.6%, P-value 0.044) with only three patients (10%) below ≤ 55% at T1. Left ventricular (LV) GLS remained impaired at T1 (-17.2 ± 2.7 vs.-17.4 ± 4, P-value 0.71) and significantly improved at T2 (-19 ± 2.6% vs. -17.4 ± 4%, P-value 0.009). LV GLS was impaired (>-18%) in 53% of patients at baseline and T1, whereas only 13% showed persistent LV GLS reduction at T2. Follow-up CMR showed LGE persistence in 33.4% of cases. CONCLUSION: Early cardiac involvement significantly improves during follow-up of MIS-C patients. However, subclinical myocardial dysfunction seems to be still detectable after 6 months of follow-up in a not negligible proportion of them.

Validation of a new intuitive software for automatic heart function analysis. An intraobserver variability study

Background/Introduction: In recent years there has been a growing interest in artificial intelligence (AI) applications in the echocardiography field. This is in order to simplify, reduce time and amplify the use of advanced analyses in the echo lab. Purpose: to compare results of the fully automated analysis and manual tracing analysis using a new intuitive software. Methods: 28 consecutive previously healthy patients less than 18 years old who were screened at our Center for cardiac evaluation within 6 months after an asymptomatic or paucisymptomatic COVID19 infection were enrolled. All they were in sinus rhythm. Standard transthoracic echocardiography (TTE) was performed for each patient using Canon Aplio i900, software 2D Wall Motion Tracking. Optimized apical 4-, 3- and 2- chamber views, mitral valve inflow pattern and LVOT Doppler interrogation were collected. Off-line data analysis of each examination was performed by both fully automated analysis (AI) and pediatric cardiologists with experience in echocardiography i.e. by manual tracing, evaluation and adjustment of the track by the operator (Echocardiographers). Operators were blinded to the AI analysis. To measure intraobserver variability, evaluations of 16 patients datasets were performed twice by both operators and AI. Results: Patients' demographic data were: age 9,8+/-4,7 years;males 22 (78%);height 134,3+/- 34,9 cm;weight 41,8+/-28,7 kg;BSA 1,2+/-0,4 mq, HR 85+/-15/min. The time taken for off-line analysis by AI and echocardiographers was 4-5 and 13-20 minutes, respectively. Reproducibility of echocardiographers' analysis was found to be excellent for left ventricle assessment (IC from 0,88 to 0,98);moderate for LVOT mean gradient (IC 0,73), RV end diastolic area (IC 0,69) and right atrial strain (IC 0,59);poor for deceleration time (IC 0,5), left ventricle strain (IC 0,49), RV FAC and strain (IC from 0,27 to 0,45). Conversely, reproducibility of the AI analysis was found to be excellent for any parameter (ICC from 0,87 to 0,99) (Table 1). About the mitralic valve inflow pattern assessment, despite the excellent reproducibility of AI analysis, the margin of error was found to be high. Particularly, a systematic error was observed with a tendency of the AI to overestimate deceleration time (DT-AI 176,6 ± 63,8 vs DTEcocardiographers 150,4 ± 24,3). Conclusion(s): Fully automated analysis is technically simple, less time consuming and highly reproducible. AI analysis of the mitralic inflow pattern should be optimized, having found a systematic error in the calculation of deceleration time. Reproducibility is the strong point of AI. This reduces the variability of manual measurements between different sonographers and at different times.

AI do it better. Reproducibility of fully automated versus manual analysis of left ventricle function using a new software

Background/Introduction: Ejection fraction (EF) is a parameter widely used in Echolab to evaluate left ventricular function. Recently, in parallel with the growing interest in artificial intelligence (AI), attemps have been made to create automated systems for EF assessment, in order to reduce time and improve the accuracy of the analysis. Purpose: to compare results of different methods of EF assessment: visual estimation (visual EF), manual and fully automated analysis. Methods: 28 consecutive pediatric patients were enrolled. This cohort of previously healthy patients was screened at our Center for cardiac evaluation within 6 months after an asymptomatic or paucisymptomatic COVID19 infection. All they were in sinus rhythm. Optimized apical 4- and 2- chamber views were collected for each patient using Canon Aplio i900. Off-line EF assessment was first evaluated visually by pediatric cardiologists with experience in echocardiography, then performed by both fully automated analysis (AI) using two different methods (Automatic Simpson -AI Simpson- and Wall Motion Tracking -AI WMT-) and pediatric cardiologists through manual tracing of endocardial border (Manual Simpson and Manual WMT respectively). Operators were blinded to the AI analysis. To measure intraobserver variability, evaluations of 16 patients' datasets were performed twice by both operators and AI. Results: Patients' demographic data were: age 9,8+/-4,7 years;males 22 (78%);height 134,3+/- 34,9 cm;weight 41,8+/-28,7 kg;BSA 1,2+/-0,4 mq, HR 85+/-15/min. The time taken for off-line analysis was 0.3-0.7 minutes, 1-1.5 minutes, 1-3 minutes and 3-4 minutes, respectively for AI WMT, AI Simpson, Manual WMT and Manual Simpson. As expected, visual EF showed high intraobserver variability and a poor reproducibility (ICC 43%). AI analysis revealed a good to excellent reproducibility (ICC from 80% to 99%, depending on the method used). WMT methods had the best reproducibility both for manual tracing of endocardial border and fully automated analysis (Table 1). The comparison between different methods (Table 2) showed a good agreement between AI Simpson and AI WMT (mean bias 2,9, from -3,2 to 9,0, ICC 86%). A moderate correlation was found between different methods of AI analysis while only poor correlation was found between manual Simpson and manual WMT (Table 2). Conclusion(s): Automatic Simpson and Wall Motion Tracking are two different fully automated methods which can be used for left ventricular function assessment. AI reproducibility is high for both methods, higher for WMT. WMT method is also less time consuming and improves reproducibility of manual tracing of endocardial borderd analysis.

Early echocardiographic and cardiac MRI findings in multisystem inflammatory syndrome in children (MIS-C)

Introduction: Multisystem Inflammatory Syndrome in Children (MISC) is a known severe condition affecting children previously exposed to SARS-CoV-2. Cardiovascular manifestations in MIS-C are quite common and include myocardial dysfunction, coronary artery dilation or aneurysms, arrhythmias, conduction abnormalities, pericarditis and valvulitis. Severe cases can present even with cardiogenic shock. To date, little is known about the very early myocardial abnormalities in pediatric patients with MIS-C. The Speckle Tracking Echocardiography (STE) and cardiac MRI (cMRI) have shown to be potential candidate for identifying regional ventricular dysfunctions in early stages of inflammatory COVID-related conditions [1,2]. Objectives: To describe the early cardiac findings in patients with MIS-C, evaluated by two advanced cardiovascular imaging, STE and cMRI. Methods: Consecutive patients with MIS-C underwent standard transthoracic echocardiography (TTE), speckle-tracking echocardiography (STE) with analysis of left ventricle (LV) global longitudinal strain (GLS) and cardiac MRI (cMRI). Clinical and laboratory data, including markers of systemic inflammation, Troponin I (TnI) and Brain Natriuretic Peptide (BNP) were also collected at onset and during follow up. All patients received intravenous immunoglobulins (IVIGs), intravenous corticosteroids (methylprednisolone) and antiplatelet therapy (aspirin). The use of biological agents (Anakinra) was reserved to patients with severe or critical illness. The need for Intensive Care Unit (ICU) was based on clinical and hemodynamic status at presentation. Results: Twenty-three patients (13M, 10F), mean age 8.1±4years (range 5.4-15.7), all with positive clinical and/or serological evidence of previous SARS-COV2 infection, entered the study. The majority (78.2%) was caucasian. All presented high degree fever, gastrointestinal symptoms and rash. Conjunctivitis and cardiovascular symptoms, as hypotension, thoracic pain or dysrhythmia, were present in 10 (43.5%). Nine children (39.1%) shared Kawasaki Disease-like symptoms. Four patients (17.4%) needed ICU admission and 3 required inotropic support. Short-term survival was 100%. All patients showed an hyperinflammatory state with elevated CRP, ESR, and D-Dimer. Tn- I was abnormal (>34 ng/L) in 15 patients (65.2%), BNP was significantly elevated in 20 (86.9%). Median time to STE evaluation was 8 days and to cMRI was 18 days since fever onset. Mean LVEF and RVEF were respectively 59±10% and 45±7%. Coronary dilation was observed in 6 (26.1%) patients. STE showed reduced mean LVGLS (-17±4.3%). LVEF on cMR was 60±13%, LGE with non-ischemic pattern was evident in 6/16 patients (37.5%) and pericardial effusion in 2 (12.5%). Conclusion: MIS-C can occur in a small but not negligible proportion of children previously affected by COVID-19 and affects the heart in a significant proportion of them. STE and cMRI were shown to be very sensitive tools to evaluate and monitor the early cardiac dysfunctions in patients with MIS-C. The elevation of myocardial necrosis markers, the myocardial injury confirmed by reduced LVGLS and presence of LGE on cMR in about a quarter of the patients support the pathogenetic hypothesis of a post-viral immuno-mediated myocarditis.

Erratum: Stereochemistry game: Creating and playing a fun board game to engage students in reviewing stereochemistry concepts - The online version (Journal of Chemical Education (2019) 96:8 (1680-1685) DOI: 10.1021/acs.jchemed.8b00897)

This paper is an addition to the article "Stereochemistry Game: Creating and Playing a Fun Board Game To Engage Students in Reviewing Stereochemistry Concepts"by JoséNunes da Silva Júnior, Daniel Esdras de Andrade Uchoa, Mary Anne Sousa Lima, and André Jalles Monteiro. With the addition, the title of the new work is "Stereochemistry Game: Creating and Playing a Fun Board Game to Engage Students in Reviewing Stereochemistry Concepts - The Online Version", and the following authors have been added: Antonio José Melo Leite Junior, Jean-Yves Winum, and Andrea Basso. The educational "Stereochemistry Game"has been extensively used face-to-face in the classroom since 2017 as an activity at the Federal University of Ceará (Brazil) and has been cited by many authors worldwide. However, all classes started occurring remotely from March 2020 due to the disruption of face-to-face activities caused by the COVID-19 pandemic. Therefore, professors and students could not use the game. This scenario motivated us to develop an online version of the game that allows students to play the game remotelyin the safety of their houses.We present this online version below. © American Chemical Society and Division of Chemical Education, Inc.

HSG400 – Design, implementation, and evaluation of a hybrid board game for aiding chemistry and chemical engineering students in the review of stereochemistry during and after the COVID-19 pandemic

This paper provides information about a hybrid multilingual (English, Portuguese, French, and Italian) game developed as an alternative learning method to the traditional problem-solving exercises model. The game comprises a physical board and a free-of-charge application for undergraduate students to review and reinforce concepts related to stereochemistry by answering questions, from a bank of 400 questions, in a ludic, competitive, and collaborative environment. Brazilian, French, and Italian undergraduate students played the game face-to-face before the disruption caused by the Covid-19 Pandemic and remotely during that. They also evaluated the game, and the quite positive results obtained from students’ self-assessment revealed that they felt the game contributed to their learning while playing. © 2021 Institution of Chemical Engineers